IFN-stimulated P2Y13 protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway
IFN-stimulated P2Y13 protects mice from viral infection by suppressing the cAMP/EPAC1 signaling pathway
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IFN 刺激的 P2Y13 通过抑制 cAMP/EPAC1 信号通路保护小鼠免受病毒感染
DOI：
10.1093/jmcb/mjy045
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发表时间：
2019
影响因子：
5.5
通讯作者：
Du Bing
中科院分区：
文献类型：
--
作者：
Zhang Chengfei;Yan Yan;He Hongwang;Wang Li;Zhang Na;Zhang Jie;Huang Hongjun;Wu Nannan;Ren Hua;Qian Min;Liu Mingyao;Du Bing
作为细胞外危险信号最重要的感受器之一，嘌呤受体在宿主防御感染中起着重要作用。然而，P2受体在病毒感染中的功能很少被探索。在这里，我们证明了P2 Y13及其配体ADP在保护宿主免受病毒感染中起重要作用。首先，我们证明，P2 Y13，作为一个典型的干扰素刺激的基因，诱导与细胞外ADP在病毒感染。最重要的是，细胞外ADP限制不同种类病毒的复制，包括水泡性口炎病毒、纽卡斯尔病病毒、单纯疱疹病毒1和鼠白血病病毒。这种保护作用依赖于P2 Y13，而不是P2 Y1或P2 Y12，它们也被认为是ADP的受体。此外，细胞外ADP通过P2 Y13偶联的Gi α亚基下调环磷酸腺苷和EPAC 1。因此，抑制或缺失EPAC 1显著消除ADP/P2 Y13介导的抗病毒活性。综上所述，我们的研究结果表明，P2 Y13和ADP在清除入侵病毒中起着关键作用，并具有作为抗病毒靶点的潜力。
Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y13 and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y13, as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y13 but not P2Y1 or P2Y12, which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregulated by extracellular ADP through the P2Y13-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y13-mediated antiviral activities. Taken together, our results show that P2Y13 and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets.